Suppression of Metastasis—A New Function for Known Proteins

Extract

In this issue of the Journal, Chang et al. (1) report the identification of an unanticipated function for connective tissue growth factor (CTGF) in the regulation of aspects of lung cancer metastasis. Their data add to a growing body of literature identifying new functions of known proteins in the regulation of metastatic growth. The functional identification of metastasis suppressor proteins requires appropriately designed in vitro,in vivo, and clinical correlative studies to assess the role of the candidate protein in the metastatic process (2). To this end, the authors present three lines of evidence to support their assertion that CTGF functions as a metastasis suppressor in lung cancer. First, ectopic expression of CTGF in adenocarcinoma cell lines that had low to undetectable levels of endogenous CTGF protein decreased Matrigel invasion in vitro. Second, complementary studies showed that ectopic expression of CTGF suppressed the ability of adenocarcinoma cells to colonize the lung in experimental metastasis assays. Finally, clinical studies showed that reduced expression of CTGF was associated with the risk of more advanced-stage disease, lymph node metastases, and shorter survival.